1. Field of the Invention
The present invention relates to an ocular insert for dispensing drugs to the eye, and, more especially, relates to an ocular insert having an improved size and shape such that the device is easily inserted into and comfortably retained within the eye, but which nevertheless is markedly resistant to expulsion therefrom.
2. Description of the Prior Art
At the present time, diseases of the eye are usually treated by applying ophthalmic drugs in liquid or ointment form. To be effective in many cases, the application of drug should be substantially continuous. Such continuous delivery of drug is not obtained through the use of liquid or ointment dosage forms, even though they be applied at intervals during the day and night. Periodic application of these dosage forms results in the eye receiving a massive, but unpredictable, amount of drug at the time of application, but the drug is washed away rapidly by tears, leaving the eye without medication until the next application. Ointment dosage forms are presently available only in unsterilized form and this too presents a problem.
At a very early time, drugs were dissolved and dispersed in a water-soluble gel of glycerinated gelatin that was shaped to the form of a lamella or eye disk. These lamellae were applied to the inner surface of the eyelid to supply drug to the eye. In use, the glycerinated gelatin vehicle dissolved rapidly to tear liquid, producing the same type of effect as liquid dosage forms. Lamellae were not a sustained-release dosage form. It is understood that same are not used in this country, although they may be used to a small extent in Europe. Further information on these water-soluble dosage forms can be found in Remington's Pharmaceutical Sciences, XIII, pages 547-8 (Mack Publishing Co., Easton, Pa. 1965); Fishburn, An Introduction to Pharmaceutical Formulation, page 116 (Pergamon Press Ltd., New York City, N.Y. 1965); and U.S. Pat. No. 273,410, Mar. 6, 1883.
U.S. Pat. No. 3,416,530, granted Dec. 17, 1968, and assigned to the assignee of this invention, is directed to the invention of a drug-dispensing ocular insert that truly acts as a depot or drug reservoir, retaining the slowly releasing drug to the eye for prolonged periods of time. Such ocular inserts are fabricated of flexible polymeric materials that are biologically inert, nonallergenic, and insoluble in tear liquid. To initiate the therapeutic program, the ocular insert is placed in the cul-de-sac of the conjunctiva between the sclera of the eyeball and the lid. Since the polymeric material from which the ocular insert is formed is insoluble in tear liquid, it retains its integrity and remains intact during the course of therapy, acting as a reservoir to continuously release drug to the eye and surrounding tissues at a rate which is not affected by dissolution or erosion of the polymeric material. On termination of the therapeutic program, the ocular insert is removed from the cul-de-sac. Thus, a single such ocular insert provides the complete ophthalmic dosage regime for a particular time period, on the order of 24 hours or longer. Frequently repeated applications, as is necessary with liquids, ointments, or water-soluble lamellae, often requiring awakening the patient during the night, are avoided.
To provide for release of ophthalmic drug from the polymeric body of the ocular insert, U.S. Pat. No. 3,416,530 describes using polymeric materials which are perforated with capillary openings. While these capillary openings are effective to release drug to the eye, they add considerable complexity to the manufacture of ocular inserts; for it is difficult to control the size of these openings in large-scale manufacturing using various polymers.
An improved drug-dispensing ocular insert, or medication-dispensing tablet for a human eyeball, which even more truly acts as a reservoir for the continuous, prolonged and controlled release of drugs to the eye, and which is not dependent upon the size and number of perforations or pores in the polymeric body of the ocular insert, is described in U.S. Pat. No. 3,618,604, granted Nov. 9, 1971, also assigned to the assignee of this invention. This '604 patented drug-delivery ocular insert to more controlledly deliver drug to the eye over a prolonged period of time, comprises a flexible body of polymeric material insoluble in tear liquid, being non-allergenic and biologically inert, and has an imperforate surface, the said body containing a drug which is dispensed to the eye in a therapeutically effective amount by diffusion through the polymeric material. This ocular insert is adapted for insertion in the cul-de-sac of the conjunctiva between the sclera of the eyeball and either the upper or lower eyelid, to be held in place against the eyeball by the pressure of the lid.
Compare also those drug-dispensing ocular inserts and accessory items therefor described in U.S. Pat. Nos. 3,626,940, 3,630,200, 3,656,481 and 3,710,795.
Nevertheless, certain individual wearers of the aforesaid drug-dispensing ocular inserts, albeit comfortable, and as same are designed to fit under but a single eyelid, have experienced varying difficulties in the regard of maintaining and retaining a given device in proper place under either the upper or lower eyelid while sleeping or during normal ocular motion. In these admittedly rare individuals, certain unspecified normal or abnormal ocular motions during daily wear, or the process known as Bell's Phenomenon while sleeping, whereby the eye has a tendency to roll upward, tend to result in the accidental expulsion of the device from the eye, thus proving annoying and/or depriving the wearer of the beneficial effects of the drug entity contained therein.